PUBLICATION
Novel TRRAP mutation causes autosomal dominant non-syndromic hearing loss
- Authors
- Xia, W., Hu, J., Ma, J., Huang, J., Wang, X., Jiang, N., Zhang, J., Ma, Z., Ma, D.
- ID
- ZDB-PUB-190625-8
- Date
- 2019
- Source
- Clinical genetics 96(4): 300-308 (Journal)
- Registered Authors
- Wang, Xu
- Keywords
- Deafness gene, Non-syndromic hearing loss, TRRAP, Zebrafish
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/genetics*
- Adaptor Proteins, Signal Transducing/metabolism
- Animals
- Animals, Genetically Modified
- Disease Models, Animal
- Exome Sequencing
- Female
- Gene Targeting
- Genes, Dominant*
- Genetic Association Studies*/methods
- Genetic Predisposition to Disease*
- Genotype
- Hearing Loss/diagnosis*
- Hearing Loss/genetics*
- Humans
- Male
- Mutation*
- Nuclear Proteins/genetics*
- Nuclear Proteins/metabolism
- Pedigree
- Phenotype
- Sequence Analysis, DNA
- Tomography, X-Ray Computed
- Zebrafish
- PubMed
- 31231791 Full text @ Clin. Genet.
Citation
Xia, W., Hu, J., Ma, J., Huang, J., Wang, X., Jiang, N., Zhang, J., Ma, Z., Ma, D. (2019) Novel TRRAP mutation causes autosomal dominant non-syndromic hearing loss. Clinical genetics. 96(4):300-308.
Abstract
Hereditary non-syndromic hearing loss is the most common inherited sensory defect in humans. More than 40 genes have been identified as causative genes for autosomal dominant non-syndromic hearing loss, but there are many other candidate genes that remain to be discovered. We aimed to identify the causative gene mutation for post-lingual progressive autosomal dominant non-syndromic hearing loss (ADNSHL) in a Chinese family. Whole-exome sequencing, bioinformatic analysis, and Sanger sequencing were used to verify the co-segregation of a novel pathogenic variant (NM_ 001244580, c.511C>T, p.Arg171Cys) in the TRansformation/tRanscription domain-Associated Protein gene associated with hearing loss in a three-generation Chinese family with ADNSHL. Additionally, three more novel variants of TRRAP were detected in 66 sporadic cases of hearing loss. Morpholino oligonucleotides knockdown and CRISPR/Cas9 knockout zebrafish were constructed to validate the genetic findings. Knockdown or knockout of TRRAP resulted in significant defects in the inner ear of zebrafish, indicating that TRRAP plays an important role in inner ear development. In conclusion, TRRAP (NM_ 001244580, c.511C>T, p.Arg171Cys) co-segregated with hearing loss in a Chinese family with autosomal dominant non-syndromic hearing loss, and TRRAP deficiency caused hearing disability in zebrafish, suggesting TRRAP is a gene associated with autosomal dominant non-syndromic hearing loss. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping